Study of podocyte biology has been hampered by limitations in available experimental models that both recapitulate the in vivo phenotypes of the podocyte and that can be readily and specifically manipulated at the molecular level. Transgenic manipulation of the podocyte represents one approach that might circumvent these limitations. The Mouse Core of the University of Michigan O'Brien Renal Center has devoted the past few years to developing the tools necessary for experimentally manipulating the mouse podocyte in situ. The behaviors of fragments of the murine Nphs1 (Nephrin) promoter-enhancer and a 2.5-kb human NPHS2 (Podocin) promoter-enhancer fragment were thoroughly characterized in transgenic mice. Two truly podocyte-specific promoters were identified that drive transgene expression in podocytes without expression in extra-renal tissues in adult or embryonic mice. Because it was judged to have the most useful characteristics, the 2.5-kb NPHS2 promoter fragment was used to create a mouse line in which Cre recombinase is expressed in a podocyte-specific pattern. Therefore, the fundamental development work has been completed that proves the feasibility of and provides the opportunity to specifically manipulate the podocyte in mice. A transgenic mouse core to support the efforts of investigators at the University of Michigan and elsewhere is proposed that would: 1. Assist Center investigators in the creation of genetically manipulated podocyte mouse models using the reagents already developed by us for this purpose; 2. Develop the transgenic tools necessary for temporal control of gene expression in a podocyte-specific fashion; and, 3. Develop the technology to "knockdown" gene expression uniquely in mouse podocytes in situ using a transgenic RNAi experimental approach.